OBJECTIVE To evaluate the diagnostic value of fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in fever of unknown origin (FUO) in a Chinese hospital. METHODS The records of 51 patients with FUO (32 men and 19 women; mean age 54 years with a range between 3 and 81 years) were analyzed retrospectively. All the patients were examined by ¹⁸F-FDG PET/CT scan and the results were compared with the final diagnosis which was established by additional procedures including pathology, laboratory examination, and clinical follow-up for more than 3 months. The t test was used for statistical analysis. RESULTS A final diagnosis was established for 48 patients, including 32 patients with infectious diseases, 9 with malignancies, and 7 with non-infectious inflammatory diseases. By FDG PET scan alone, the rates of true positive, false positive, false negative, and true negative were 52.9%, 27.5%, 17.6%, and 2.0%, respectively. By FDG PET/CT scan, the rates of true positive, false positive, false negative, and true negative were 70.6%, 27.5%, 2.0%, and 0, respectively. ¹⁸F-PET/CT had a sensitivity of 97.3% (36/37), specificity of 0 (0/14), and accuracy of 70.6% (36/51) in FUO, especially a high sensitivity and accuracy of 100% (9/9) in the diagnosis of malignant tumor. Moreover, the maximum standardized uptake value (SUVmax) in tumor was significant higher than that in infection (3.7 ± 2.7 vs. 7.7 ± 3.5, P=0.001, t=3.6), which implied that SUVmax might be useful in differential diagnosis in FUO. CONCLUSIONS FDG PET/CT is a valuable imaging tool for the identification and location of the potential lesion in FUO and is helpful for the etiological diagnosis, especially in the diagnosis of malignant lesions.